Pharmacological evaluation of Natural Sea Salt against doxorubicin induced cardiac toxicity via Gut Microbiome

Abstract

Abstract Cardiovascular complications including cardiac toxicity pose a major health threat worldwide. These complications can be handled by reducing the associated risk factors including diet. Gut microbiome is prominently associated with cardiovascular diseases. The present study demonstrates how the gut microbiota, under the effect of table salt and natural sea salt, modulates doxorubicin-induced cardiac toxicity. Experimental animals were divided into six groups (n = 6) as: Group I. Normal control (NC); Group II: table salt (0.3%) (NTS); Group III: natural sea salt (0.3%) (NSS.); Group IV: Doxorubicin-induced cardiac toxicity control (2mg/kg) (DC); Group V:DC + Table salt (0.3%) (DTS.); and Group VI: DC + Natural sea salt (0.3%) (DSS). CKMB, CRP, lipid profile was assayed in serum, GUT microbiota in stool, and histopathological variations in heart tissues were studied. Significant alterations were observed in the analytical values of blood parameters in the doxorubicin versus the normal control group. Also, a significant variation was observed in DTS and DSS groups for CKMB (p < 0.001), CRP (p < 0.01; p < 0.05), TC, TG, LDL (p < 0.0001) and HDL (p < 0.05, p < 0.01) respectively, when compared with DC group. Presence of gut microbes were identified in the stool samples. The population of Proteobacteria and Spirochetes were significantly lowered the DC group as compared to all other groups. However, the treatment with the sea salt increased the richness of this phylum to 36-fold, while table salt increased only by 9-fold. The change in microbial population is a direct marker for cardiac toxicity, which was highly prevented by sea salt as compared to table salt. Histopathological alterations in cellular architecture of the heart reflect a marked effect of the salts on it. Our observations suggest that a diet with natural sea salt demonstrated a significant protection to cardiac toxicity that may have initiated via inflammation after doxorubicin injury compared to the table salt.